Pluvicto (Lutetium Lu 177 Vipivotide Tetraxetan)

PLUVICTO is indicated for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibitor (ARPI) therapy, and

• are considered appropriate to delay taxane-based chemotherapy, or
• have received prior taxane-based chemotherapy.

Injection: 1,000 MBq/mL (27 mCi/mL) of lutetium Lu 177 vipivotide tetraxetan as a clear and colorless to slightly yellow solution in a single-dose vial.

The safety and efficacy of PLUVICTO have not been established in females. Based on its mechanism of action, PLUVICTO can cause fetal harm

• Risk From Radiation Exposure
  : Minimize radiation exposure during and after treatment with PLUVICTO consistent with institutional good radiation safety practices and patient treatment procedures. Ensure patients increase oral fluid intake and advise patients to void as often as possible to reduce bladder radiation. (
  5.1     Risk From Radiation Exposure

  PLUVICTO contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer.

  Minimize radiation exposure to patients, medical personnel, and others during and after treatment with PLUVICTO consistent with institutional good radiation safety practices, patient treatment procedures, Nuclear Regulatory Commission patient-release guidance, and instructions to the patient for follow-up radiation protection at home.

  Ensure patients increase oral fluid intake and advise patients to void as often as possible to reduce bladder radiation.

  Before the patient is released, inform patients about the necessary radioprotection precautions to follow to minimize radiation exposure to others

  [see Patient Counseling Information (17)]

  .

  After each administration of PLUVICTO, advise patients to:

  • Limit close contact (less than 3 feet) with others for 2 days or with children and pregnant women for 7 days.
  • Refrain from sexual activity for 7 days.
  • Sleep in a separate room from others for 3 days, from children for 7 days, or from pregnant women for 15 days.
  )
• Myelosuppression
  : Perform complete blood counts. Withhold, reduce dose, or permanently discontinue PLUVICTO based on severity. (
  2.4     Dosage Modifications for Adverse Reactions

  Recommended dosage modifications of PLUVICTO for adverse reactions are provided in Table 1. Management of adverse reactions may require temporary dose interruption, dose reduction or permanent discontinuation of treatment with PLUVICTO. If a treatment delay due to an adverse reaction persists for > 4 weeks, consider permanent discontinuation of PLUVICTO. The dose of PLUVICTO may be reduced by 20% to 5.9 GBq (160 mCi) once; do not re-escalate dose. If a patient has further adverse reactions that would require an additional dose reduction, treatment with PLUVICTO must be discontinued.

  Table 1: Recommended Dosage Modifications of PLUVICTO for Adverse Reactions

  Abbreviations: CLcr, creatinine clearance; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ULN, upper limit of normal. Grading according to most current Common Terminology Criteria for Adverse Events (CTCAE).
  Adverse reaction	Severity	Dosage modification
  Myelosuppression (Anemia, thrombocytopenia, leukopenia, or neutropenia) [see Warnings and Precautions (5.2)]	Grade 2	Withhold PLUVICTO until improvement to Grade 1 or baseline.
  	Grade ≥ 3	Withhold PLUVICTO until improvement to Grade 1 or baseline. Reduce PLUVICTO dose by 20% to 5.9 GBq (160 mCi).
  	Recurrent Grade ≥ 3 myelosuppression after one dose reduction	Permanently discontinue PLUVICTO.
  Renal toxicity [see Warnings and Precautions (5.3)]	Defined as: Confirmed serum creatinine increase (Grade ≥ 2) Confirmed CLcr < 30 mL/min; calculate using Cockcroft-Gault with actual body weight	Withhold PLUVICTO until improvement.
  	Defined as: Confirmed ≥ 40% increase from baseline serum creatinine and Confirmed > 40% decrease from baseline CLcr; calculate using Cockcroft-Gault with actual body weight	Withhold PLUVICTO until improvement or return to baseline. Reduce PLUVICTO dose by 20% to 5.9 GBq (160 mCi).
  	Grade ≥ 3 renal toxicity	Permanently discontinue PLUVICTO.
  	Recurrent renal toxicity after one dose reduction	Permanently discontinue PLUVICTO.
  Dry mouth [see Adverse Reactions (6.1)]	Grade 2	Withhold PLUVICTO until improvement or return to baseline. Consider reducing PLUVICTO dose by 20% to 5.9 GBq (160 mCi).
  	Grade 3	Withhold PLUVICTO until improvement or return to baseline. Reduce PLUVICTO dose by 20% to 5.9 GBq (160 mCi).
  	Recurrent Grade 3 dry mouth after one dose reduction	Permanently discontinue PLUVICTO.
  Gastrointestinal toxicity [see Adverse Reactions (6.1)]	Grade ≥ 3 (not amenable to medical intervention)	Withhold PLUVICTO until improvement to Grade 2 or baseline. Reduce PLUVICTO dose by 20% to 5.9 GBq (160 mCi).
  	Recurrent Grade ≥ 3 gastrointestinal toxicity after one dose reduction	Permanently discontinue PLUVICTO.
  Fatigue [see Adverse Reactions (6.1)]	Grade ≥ 3	Withhold PLUVICTO until improvement to Grade 2 or baseline.
  Electrolyte or metabolic abnormalities [see Adverse Reactions (6.1)]	Grade ≥ 2	Withhold PLUVICTO until improvement to Grade 1 or baseline.
  Other non-hematologic toxicity [see Adverse Reactions (6.1)]	Any unacceptable toxicity	Permanently discontinue PLUVICTO.
  	Any adverse reaction that requires treatment delay of > 4 weeks	Permanently discontinue PLUVICTO.
  	Any recurrent Grade 3 or 4 or persistent and intolerable Grade 2 adverse reaction after one dose reduction	Permanently discontinue PLUVICTO.
  ,
  5.2     Myelosuppression

  PLUVICTO can cause severe and life-threatening myelosuppression, including anemia, thrombocytopenia, leukopenia, and neutropenia.

  In the PSMAfore study, Grade 3 or 4 decreased hemoglobin (7%), decreased leukocytes (4.4%), decreased neutrophils (3.5%), and decreased platelets (2.7%) occurred in patients treated with PLUVICTO. One death occurred due to bone marrow failure during long-term follow-up in a patient who received PLUVICTO.

  In the VISION study, Grade 3 or 4 decreased hemoglobin (15%), decreased platelets (9%), decreased leukocytes (7%), and decreased neutrophils (4.5%) occurred in patients treated with PLUVICTO. Grade ≥ 3 pancytopenia occurred in 1.1% (which includes two fatal events) of patients treated with PLUVICTO. Two deaths (0.4%) occurred due to intracranial hemorrhage and subdural hematoma in association with thrombocytopenia, one death (0.2%) occurred due to sepsis and concurrent neutropenia, and one death (0.2%) occurred due to bone marrow failure.

  Perform complete blood counts before and during treatment with PLUVICTO. Withhold, reduce dose, or permanently discontinue PLUVICTO based on the severity of myelosuppression

  [see Dosage and Administration (2.4)]

  .
  )
• Renal Toxicity
  : Advise patients to remain well hydrated and to urinate frequently. Perform kidney function laboratory tests. Withhold, reduce dose, or permanently discontinue PLUVICTO based on severity. (
  2.4     Dosage Modifications for Adverse Reactions

  Recommended dosage modifications of PLUVICTO for adverse reactions are provided in Table 1. Management of adverse reactions may require temporary dose interruption, dose reduction or permanent discontinuation of treatment with PLUVICTO. If a treatment delay due to an adverse reaction persists for > 4 weeks, consider permanent discontinuation of PLUVICTO. The dose of PLUVICTO may be reduced by 20% to 5.9 GBq (160 mCi) once; do not re-escalate dose. If a patient has further adverse reactions that would require an additional dose reduction, treatment with PLUVICTO must be discontinued.

  Table 1: Recommended Dosage Modifications of PLUVICTO for Adverse Reactions

  Abbreviations: CLcr, creatinine clearance; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ULN, upper limit of normal. Grading according to most current Common Terminology Criteria for Adverse Events (CTCAE).
  Adverse reaction	Severity	Dosage modification
  Myelosuppression (Anemia, thrombocytopenia, leukopenia, or neutropenia) [see Warnings and Precautions (5.2)]	Grade 2	Withhold PLUVICTO until improvement to Grade 1 or baseline.
  	Grade ≥ 3	Withhold PLUVICTO until improvement to Grade 1 or baseline. Reduce PLUVICTO dose by 20% to 5.9 GBq (160 mCi).
  	Recurrent Grade ≥ 3 myelosuppression after one dose reduction	Permanently discontinue PLUVICTO.
  Renal toxicity [see Warnings and Precautions (5.3)]	Defined as: Confirmed serum creatinine increase (Grade ≥ 2) Confirmed CLcr < 30 mL/min; calculate using Cockcroft-Gault with actual body weight	Withhold PLUVICTO until improvement.
  	Defined as: Confirmed ≥ 40% increase from baseline serum creatinine and Confirmed > 40% decrease from baseline CLcr; calculate using Cockcroft-Gault with actual body weight	Withhold PLUVICTO until improvement or return to baseline. Reduce PLUVICTO dose by 20% to 5.9 GBq (160 mCi).
  	Grade ≥ 3 renal toxicity	Permanently discontinue PLUVICTO.
  	Recurrent renal toxicity after one dose reduction	Permanently discontinue PLUVICTO.
  Dry mouth [see Adverse Reactions (6.1)]	Grade 2	Withhold PLUVICTO until improvement or return to baseline. Consider reducing PLUVICTO dose by 20% to 5.9 GBq (160 mCi).
  	Grade 3	Withhold PLUVICTO until improvement or return to baseline. Reduce PLUVICTO dose by 20% to 5.9 GBq (160 mCi).
  	Recurrent Grade 3 dry mouth after one dose reduction	Permanently discontinue PLUVICTO.
  Gastrointestinal toxicity [see Adverse Reactions (6.1)]	Grade ≥ 3 (not amenable to medical intervention)	Withhold PLUVICTO until improvement to Grade 2 or baseline. Reduce PLUVICTO dose by 20% to 5.9 GBq (160 mCi).
  	Recurrent Grade ≥ 3 gastrointestinal toxicity after one dose reduction	Permanently discontinue PLUVICTO.
  Fatigue [see Adverse Reactions (6.1)]	Grade ≥ 3	Withhold PLUVICTO until improvement to Grade 2 or baseline.
  Electrolyte or metabolic abnormalities [see Adverse Reactions (6.1)]	Grade ≥ 2	Withhold PLUVICTO until improvement to Grade 1 or baseline.
  Other non-hematologic toxicity [see Adverse Reactions (6.1)]	Any unacceptable toxicity	Permanently discontinue PLUVICTO.
  	Any adverse reaction that requires treatment delay of > 4 weeks	Permanently discontinue PLUVICTO.
  	Any recurrent Grade 3 or 4 or persistent and intolerable Grade 2 adverse reaction after one dose reduction	Permanently discontinue PLUVICTO.
  ,
  5.3     Renal Toxicity

  PLUVICTO can cause severe renal toxicity.

  In the PSMAfore study, Grade 3 or 4 acute kidney injury (1.3%) occurred in patients treated with PLUVICTO. In the VISION study, Grade 3 or 4 acute kidney injury (3.4%) occurred in patients treated with PLUVICTO.

  Advise patients to remain well hydrated and to urinate frequently before and after administration of PLUVICTO. Perform kidney function laboratory tests, including serum creatinine and calculated creatinine clearance (CLcr), before and during treatment with PLUVICTO. Withhold, reduce dose, or permanently discontinue PLUVICTO based on the severity of renal toxicity

  [see Dosage and Administration (2.4)]

  .
  )
• Embryo-Fetal Toxicity
  : Can cause fetal harm. Advise males with female partners of reproductive potential to use effective contraception. (
  5.4     Embryo-Fetal Toxicity

  The safety and efficacy of PLUVICTO have not been established in females. Based on its mechanism of action, PLUVICTO can cause fetal harm

  [see Clinical Pharmacology (12.1)]

  . No animal studies using lutetium Lu 177 vipivotide tetraxetan have been conducted to evaluate its effect on female reproduction and embryo-fetal development; however, radioactive emissions, including those from PLUVICTO, can cause fetal harm. Advise males with female partners of reproductive potential to use effective contraception during treatment with PLUVICTO and for 14 weeks after the last dose

  [see Use in Specific Populations (8.1, 8.3)]

  .
  ,
  8.1     Pregnancy

  Risk Summary

  The safety and efficacy of PLUVICTO have not been established in females. Based on its mechanism of action, PLUVICTO can cause fetal harm

  [see Clinical Pharmacology (12.1)]

  . There are no available data on PLUVICTO use in pregnant females. No animal studies using lutetium Lu 177 vipivotide tetraxetan have been conducted to evaluate its effect on female reproduction and embryo-fetal development; however, all radioactive emissions, including those from PLUVICTO, can cause fetal harm.
  ,
  8.3     Females and Males of Reproductive Potential

  Contraception

  Males

  Advise males with female partners of reproductive potential to use effective contraception during treatment with PLUVICTO and for 14 weeks after the last dose

  [see Clinical Pharmacology (12.1), Nonclinical Toxicology (13.1)]

  .

  Infertility

  The recommended cumulative dose of 44.4 GBq of PLUVICTO results in a radiation absorbed dose to the testes within the range where PLUVICTO may cause temporary or permanent infertility.
  )
• Infertility
  : PLUVICTO may cause temporary or permanent infertility. (
  5.5     Infertility

  PLUVICTO may cause infertility in males. The recommended cumulative dose of 44.4 GBq of PLUVICTO results in a radiation absorbed dose to the testes within the range where PLUVICTO may cause temporary or permanent infertility

  [see Use in Specific Populations (8.3)]

  .
  ,
  8.3     Females and Males of Reproductive Potential

  Contraception

  Males

  Advise males with female partners of reproductive potential to use effective contraception during treatment with PLUVICTO and for 14 weeks after the last dose

  [see Clinical Pharmacology (12.1), Nonclinical Toxicology (13.1)]

  .

  Infertility

  The recommended cumulative dose of 44.4 GBq of PLUVICTO results in a radiation absorbed dose to the testes within the range where PLUVICTO may cause temporary or permanent infertility.
  )